Potentiation of Butylated Hydroxytoluene-induced Acute Lung Damage by Oxygen

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Abstract
Changes in cell proliferation and in collagen synthesis were studied in young adult male BALB/c mice injected intraperitoneally with 400 mg/kg of butylated hydroxytoluene (BHT) in corn oil or corn oil alone and immediately exposed to 70% oxygen or air for 6 days. Mice received [3H]thymidine either as a single injection 90 min before being killed or as a continual infusion via an osmotic minipump. Autoradiography was done 2 to 14 days after BHT injection, and cell kinetic studies were performed. In a similar experiment, mice were injected intraperitonealiy with [3H]proline 3 h before being killed, and type l/type III collagen ratio in newly synthesized lung collagen was determined. We found that exposure to 70% oxygen immediately after the administration of BHT initially delayed the epithelial cell proliferation and the decrease in the percentage of newly synthesized type III collagen that occurred after BHT alone. Once the animals were removed from oxygen there was a compensatory burst of cell proliferation and a precipitous drop in the percentage of newly synthesized type III collagen. The proliferating cell population after removal from oxygen was primarily interstitial and not epithelial. When exposure to oxygen was delayed, cell proliferation was similar to that seen after BHT injection alone.